Species Heterogeneity in the Metabolic Processing of Benzo(A)Pyrene

摘要

The drug metabolizing microsomal mixed-function oxidase (MFO) is a complex of enzymes required for the activation and detoxification of xenobiotics. Metabolism studies with many chemical carcinogens and mutagens in large numbers of different cell types and species and tissues have shown a remarkable qualitative similarity in the metabolic products formed by this enzyme complex. However, there is considerable variance from a quantitative aspect at several important levels in this biochemical process. Furthermore, within a given species, there can be major strain differences, not only in hepatic tissue, which is the major site for mixed function oxidase activity, but in all the organs and tissues throughout the body. Since the MFO system is a complex of both activating and detoxifying enzymes, one may find variable levels of mixed function oxidase and the detoxification epoxide hydrase within a given activation system. This in turn may dictate whether there will be a high or low relative level of reactive electrophile available for interaction with critical target sites. Beno(a)pyrene (B(a)P), a major environmental carcinogen and mutagen, has been used as the paradigm for environmental chemical carcinogens. We have studied the metabolism of B(a)P in human and rodent cell lines to determine quantitative and qualitative variance between species.